We have recently demonstrated that: (1) thrombin-induced binding of von Willebrand factor (vWF) is deficient in Glanzmann's thrombasthenia; 2) ristocetin-induced vWF-platlet interaction is heightened in type IIB von Willebrand's disease; and 3) normal vWF binds spontaneously to platelets in "Platelet type" von Willebrand's disease. These observations rais new questions concerning the molecular basis of vWF-platelet interaction which we propose to investigate in the following manner. 1) The characteristics of thrombin-induced and ristocetin-induced platelet binding of individual vWF multimers or group of multimers will be analyzed to determine the effect of ligand heterogeneity and/or binding site heterogeneity on this interaction. 2) The nature of platelet binding site(s) exposed by different stimuli (thrombin and ristocetin) will be investigated using monoclonal antibodies to platelet membrane glycoproteins and studying patients with congenital defects of these lycoproteins. 3) The presumably abnormal vWF platelet binding site described in pseudo or Platelet-type von Willebrand's disease will be characterized and its relationship with binding site(s) exposed on normal platelets will be established. 4) The possibility that common mechanisms are involved in the expression of platelet binding sites for vWFm fibrinogen and fibronectin, as suggested by studies in Glanzmann's thrombasthenia, will be investigated using different monoclonal antibodies and direct analysis of interaction or competition between these purified ligands. 5) Monoclonal antibodies to vWf will be used to identify relevant epitopes involved in interaction with platelets and their effect on platelet function in vivo will be studied in animal models (baboons). 6) The abnormal vWf from various subtypes of von Willebrand's disease will be analyzed in respect to thrombin-induced binding to establish correlations between structural and functional defects. 7) The functional role of platelet vWF will be compared to that of circulating vWF. Thrombin-induced expression of platelet vWF on the platelet membrane will be studied in patients with von Willebrand's disease to evaluate its possible pathogenetic role in the bleeding abnormality.